The primary theme of this proposal is the further development of samarium(II) iodide (SmI2) and related reagents as highly selective reductive coupling agents for organic synthesis. Samarium(II) iodide promotes reactions with many functional groups of interest to synthetic organic chemists, and in this context this soluble one electron reductant has been found to be a.remarkably versatile reagent. The Sm(III) ion generated during the course of reductive coupling reactions is a highly oxophilic species. This Lewis acid can therefore be utilized as a template upon which to control stereochemistry. The combination of these features makes SmI2 highly complementary in many respects to other, perhaps more traditional, reductants such as Mg, Zn, Cr(II), and dissolving metal reductants. The unique combination of characteristics exhibited by SmI2 permits chemical transformations that are difficult, if not impossible, to achieve by other currently available means. The emphasis of our research will be in continuing the exploration of unconventional reactivity and selectivity patterns with SmI2, thereby facilitating the rapid and efficient synthesis of complex organic structures from relatively simple substrates. Several distinct areas have been targeted for study. An investigation of intramolecular nucleophilic acyl substitution reactions of halo- substituted carboxylic acid derivatives will be completed. Studies will be initiated to explore ketyl-olefin coupling reactions and subsequent transformations of the intermediates generated from them. Highlights of these studies will include the synthesis of eight-membered carbocycles, as well as an examination of five- through eight-membered oxygen and nitrogen heterocycle synthesis. One of the unique features of SmI2 is its ability to sustain sequential radical and carbanionic reactions in one-pot processes. Much of the proposal centers on this important feature of this versatile reductant. Over the past few years a tremendous database has been established which permits one to reliably predict relative reactivity of various organic functional groups with SmI2. This knowledge will be utilized to sequence organic reactions in polyfunctional organic substrates. This sequencing will permit formation of multiple carbon- carbon bonds in a single-pot process, in most instances with complete control of stereochemistry over several stereocenters. Finally, while past experience has demonstrated that SmI2 is an excellent reductant for many of the processes under study, development and employment of other SmX2 reducing agents that may exhibit enhanced reactivity or other desirable properties will also be undertaken. The types of studies outlined in this proposal are fundamental in nature, and yet may have direct application in the pharmaceutical industry for the efficient synthesis of pharmacologically active materials, analogues, metabolites, and other intermediates required for studies in drug developme .